Background Behçet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains speculative. Since the identification of HLA-B*5101 (and more recently of MICA) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled.
Objective To carry out a genome-wide association study (GWAS) of BD.
Methods 300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23 465 microsatellites (MS) covering the entire genome.
Results The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (HLA) class I region itself. Although one of these was clearly reminiscent of the association with HLA-B, the second, not in linkage disequilibrium with the former, was in the telomeric side of the class I region and remained to be formally identified. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: HLA-B*5101 and HLA-A*26.
Conclusions This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: HLA-B and HLA-A.
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Funding This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a grant from the Ministry of Health, Labour and Welfare, Japan; and a grant from the Johnson & Johnson K.K. Vision Care Company. SB's laboratory is supported by the ‘Agence Nationale pour la Recherche’ (ANR), the ‘Fédération des Maladies Orphelines’ and the ‘Association française de la maladie de Behçet’.
Competing interests None.
Ethics approval This study was conducted with the approval of the respective ethics authorities within each recruiting institution-that is, Yokohama City University, Hokkaido University, Kurume University, Yuasa Eye Clinic and Fujioka Eye Hospital; all in Japan.
Provenance and peer review Not commissioned; externally peer reviewed.